The pulmonary alveolar macrophage (AM) comprises >85% of cells recovered from the lung by bronchoalveolar lavage in all species studied. B-cells, T-cells, other macrophages and dendritic cells, the latter of which exhibit potent accessory cell function, can also be recovered from lung tissue. How these cells function independently and together to protect the lung against potential immunopathology resulting from continuous exposure to environmental antigens is not understood. We have shown that .AM function as regulating elements in the induction and expression of a variety of immune responses. Our studies strongly suggest that within the AM population there are cells that serve to down-regulate immunological processes occurring in the respiratory tract. Using an in vitro murine model system, experiments have been designed to extend our previous observations on the immunoregulatory functions of AM so as to provide a clear understanding of their role in protecting the lung against potential immunopathology. We propose to define the cellular, biochemical and molecular mechanisms by which Am elicit their immunoregulatory functions. The specific aims are: 1) to determine the cellular basis of AM-mediated regulation by ascertaining the cellular source of the suppressor factor (SF) involved, and by determining if AM-- mediated suppression is isotype-specific; 2) to determine the biochemical basis of AM-mediated regulation through the use of homogeneous cell populations (i.e., MH-S AM cell line and T-cell clones developed in this laboratory) to produce, purify and characterize the SF in regard to its biochemical and physical properties as well as to generate antibodies which can be used to modulate its function; 3) to determine the molecular basis of AM-mediated regulation by cloning the gene that encodes for the production of the SF and studying its expression and function. Results from these studies should provide insight into the mechanism(s) by which AM protect the lung from immunopathology.